Limb and skin abnormalities in mice lacking IKKalpha

K Takeda; O Takeuchi; T Tsujimura; S Itami; O Adachi; T Kawai; H Sanjo; K Yoshikawa; N Terada; S Akira

doi:10.1126/science.284.5412.313

Limb and skin abnormalities in mice lacking IKKalpha

Science. 1999 Apr 9;284(5412):313-6. doi: 10.1126/science.284.5412.313.

Authors

K Takeda¹, O Takeuchi, T Tsujimura, S Itami, O Adachi, T Kawai, H Sanjo, K Yoshikawa, N Terada, S Akira

Affiliation

¹ Department of Biochemistry and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

PMID: 10195895
DOI: 10.1126/science.284.5412.313

Abstract

The gene encoding inhibitor of kappa B (IkappaB) kinase alpha (IKKalpha; also called IKK1) was disrupted by gene targeting. IKKalpha-deficient mice died perinatally. In IKKalpha-deficient fetuses, limb outgrowth was severely impaired despite unaffected skeletal development. The epidermal cells in IKKalpha-deficient fetuses were highly proliferative with dysregulated epidermal differentiation. In the basal layer, degradation of IkappaB and nuclear localization of nuclear factor kappa B (NF-kappaB) were not observed. Thus, IKKalpha is essential for NF-kappaB activation in the limb and skin during embryogenesis. In contrast, there was no impairment of NF-kappaB activation induced by either interleukin-1 or tumor necrosis factor-alpha in IKKalpha-deficient embryonic fibroblasts and thymocytes, indicating that IKKalpha is not essential for cytokine-induced activation of NF-kappaB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cytoplasm / metabolism
DNA-Binding Proteins / metabolism
Epidermal Cells
Epidermis / embryology*
Epidermis / metabolism
Extremities / embryology*
Extremities / growth & development
Gene Expression Regulation, Developmental
Gene Targeting
I-kappa B Kinase
I-kappa B Proteins
Interleukin-1 / pharmacology
Keratinocytes / cytology
Keratinocytes / metabolism
Limb Buds / enzymology
Limb Deformities, Congenital / enzymology*
Limb Deformities, Congenital / genetics
Mice
Myogenic Regulatory Factors*
NF-kappa B / metabolism
Nuclear Proteins / genetics
Phosphorylation
Protein Serine-Threonine Kinases / deficiency
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Skin Abnormalities / enzymology*
Skin Abnormalities / genetics
Transcription Factor RelA
Tumor Necrosis Factor-alpha / pharmacology
Twist-Related Protein 1

Substances

DNA-Binding Proteins
I-kappa B Proteins
Interleukin-1
Myogenic Regulatory Factors
NF-kappa B
Nuclear Proteins
Transcription Factor RelA
Tumor Necrosis Factor-alpha
Twist-Related Protein 1
Twist1 protein, mouse
Protein Serine-Threonine Kinases
Chuk protein, mouse
I-kappa B Kinase
Ikbkb protein, mouse
Ikbke protein, mouse